The goal of our research is to understand how nucleic acids and their constituents interact with one another, with proteins and with drugs. Specifically, we continue to examine the role of sequence, chemical modifications and environment on the structures and on their interactions. The principal method of analysis is x-ray crystallographic studies of the structures of selected oligonucleotides and complexes of oligonucleotides with drugs. The oligonucleotides chosen contain biologically relevant sequences, mutagenic and carcinogenic lesions, and features that allow for the formation of hairpins and cruciforms. We will complete the analysis of a complex between the chemotherapeutic drug, Actinomycin D and a small fragment of DNA to which it is known to bind. We will also continue pilot studies on the nucleotide binding enzyme, AMP nucleosidase with the goal of producing crystals suitable for a full x-ray crystallographic analysis.